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Compositions and methods for restoring sensitivity to treatment with HER2 antagonists

a technology of antagonists and compositions, applied in the field of compositions and methods for restoring sensitivity to treatment with her2 antagonists, can solve the problems of poor outcome and decreased survival of patients

Active Publication Date: 2010-03-09
A & G PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Overexpression of the c-erbB2 oncogene has been linked to poor outcome and decreased survival for patients.
However, only 25% of the patients treated with Herceptin® or any other antibody to c-erbB2 / HER2 are responsive to this therapy.

Method used

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  • Compositions and methods for restoring sensitivity to treatment with HER2 antagonists
  • Compositions and methods for restoring sensitivity to treatment with HER2 antagonists
  • Compositions and methods for restoring sensitivity to treatment with HER2 antagonists

Examples

Experimental program
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Effect test

examples

PCDGF Confers Resistance to the Antineoplastic Effects of HER2 Antagonist Therapy

Methods and Materials

Preparation of Stable Transfectants

[0080]To investigate the role of PCDGF in HER2 antagonist resistance of c-erbB2 overexpressing cells, MCF-7 breast cancer cells were stably transfected with pcDNA3 / erbB2 expression vector (see FIG. 2) by the calcium phosphate method. A c-erbB2 overexpressing clone (erbB2.c1) was selected, and used for the subsequent stable transfection with pSecTag / PCDGF expression vector. Among the clones overexpressing both c-erbB2 and PCDGF, D.c2 clone was selected and further examined in comparison to single erbB2 overexpressing cells (see FIGS. 5, 6 and 7). Clones were established in the presence of Zeocin and / or G418.

Cell Proliferation Assay

[0081]The cells were plated in DMEF / F12 containing 5% FBS at 8×104 cells / well. After 24 hours of incubation, the cells were washed and fresh PFMEM was added along with various treatments. The cells were counted using a hem...

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Abstract

Methods and compositions for restoring growth inhibition sensitivity to a tumor cell resistant to growth inhibition by HER2 antagonists. The methods involve administering a PCDGF antagonist to the cell in an amount effective to stimulate or restore growth inhibition sensitivity to HER2 antagonists. The invention also provides treatment regimens, and therapeutic compositions comprising an HER2 antagonist and a PCDGF antagonist.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application Nos. 60 / 491,536 filed Aug. 1, 2003 and 60 / 547,791 filed Feb. 27, 2004, both of which are hereby incorporated by reference in their entireties.[0002]The following U.S. Patents and U.S. Patent Publications are expressly incorporated by reference herein in their entireties: U.S. Pat. Nos. 6,720,159; 6,309,826; U.S. Patent Publication No. 2003 / 0099646; U.S. Patent Publication No. 2003 / 0215445; and U.S. Patent Publication No. 2002 / 0025543.REFERENCES[0003]Several publications are referenced herein. Full citations for these publications are provided below. The disclosures of these publications are hereby incorporated herein by reference in their entirety, unless otherwise noted.BACKGROUND OF THE INVENTION[0004]Approximately 25-30% of breast cancer patients overexpress the proto-oncoprotein and cell surface receptor c-erbB2 (human epidermal growth factor receptor 2 protein), also...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K39/395A61KC07K16/22C07K16/32G01N33/574
CPCC07K16/22G01N33/574C07K16/32C07K2316/96C07K2317/73A61P13/08A61P31/00A61P35/00A61P35/02A61P43/00
Inventor SERRERO, GINETTE
Owner A & G PHARMA
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